Project description:MYST4 (QKF/KAT6B/MORF) is an important regulator of brain development and function through its regulation of gene expression. Genetic targets of MYST4 are currently unknown. We have therefore carried out microarrays comparing gene expression in wild type and Qkf mouse tissues, namely the dorsal cortex and E12.5 dorsal telencephalon, to elucidate genetic targets of MYST4. RNA was extracted for hybridization to arrays from 3 pairs of wild type and Qkf gt/gt mutant adult dorsal corticies and 3 pairs of wild type and Qkf gt/gt mutant E12.5 dorsal telencephalons
Project description:MYST4 (QKF/KAT6B/MORF) is an important regulator of brain development and function through its regulation of gene expression. Genetic targets of MYST4 are currently unknown. We have therefore carried out microarrays comparing gene expression in wild type and Qkf mouse tissues, namely the dorsal cortex and E12.5 dorsal telencephalon, to elucidate genetic targets of MYST4.
Project description:High histone acetylation is associated with high transcriptional activity. The lysine acetyltransferase KAT6B is known to be required for histone acetylation and KAT6B is essential for normal brain development. In this study we examined the effects of loss and gain of KAT6B on gene expression in the developing cerebral cortex. We isolated RNA from the dorsal telencephalon of embryonic day 12.5 embryos, which is the primordium of the cerebral cortex, and from the E15.5 foetal cortex of mouse embryos and foetuses that lacked KAT6B or overexpressed KAT6B. Genes required for brain development and neuronal differentiation were downregulated in Kat6b null tissues and upregulated in Kat6b transgenic overexpressing tissue.
Project description:High histone acetylation is associated with high transcriptional activity. The lysine acetyltransferase KAT6B is known to be required for histone acetylation and KAT6B is essential for normal brain development. In this study we examined the effects of loss and gain of KAT6B on gene expression in forebrain neural stem and progenitor cells (NSPCs). We isolated NSPCs from the dorsal telencephalon of embryonic day 12.5 embryos, which is the primordium of the cerebral cortex, from mouse embryos that lacked KAT6B or overexpressed KAT6B. We cultured the cells in vitro for 3 to 5 passages before isolating RNA for library production and RNA-sequencing. We found that genes required for neuronal differentiation and brain development were downregulated in Kat6b null cells and upregulated in Kat6b transgenic overexpressing cells.
Project description:Zinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon. We compared gene expression profiles of rostral forebrains, which contain the telencephalon and the rostral part of the diencephalon, from embryonic day (E) 9.5, E10.5, and E12.5 wild-type control and Fezf1-/- Fezf2 -/- mouse embryos.
Project description:Zinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon. We compared gene expression profiles of rostral forebrains, which contain the telencephalon and the rostral part of the diencephalon, from embryonic day (E) 9.5, E10.5, and E12.5 wild-type control and Fezf1-/- Fezf2 -/- mouse embryos. The forebrain rostral to the caudal limit of the lateral ventricles was isolated manually from E9.5, E10.5, and E12.5 wild-type and Fezf1-/- Fezf2-/- mice. Total RNAs were isolated by Separsol-RNA I and were used for microarray analyses.
Project description:Heterozygous mutations in the histone acetyltransferase gene KAT6B (MYST4/MORF/QKF) cause cognitive disorders. Congruently, KAT6B is required for brain development, neural stem cell self-renewal and neuronal differentiation in mice. Despite the clear requirement for KAT6B in brain development, its molecular roles remain unexplored. Here we use ATAC sequencing to determine the effects of loss or gain of KAT6B on DNA accessiblity.
Project description:The Otx2 homeobox transcription factor is essential for gastrulation and early neural development. We generated Otx2 conditional knockout (cKO) mice to investigate its roles in telencephalon development after E9.0. We conducted transcriptional profiling and in situ hybridization to identify genes de-regulated in Otx2 cKO ventral forebrain. In parallel, we used ChIP-seq to identify enhancer elements, OTX2 binding motif, and which de-regulated genes are likely direct targets of Otx2 transcriptional regulation. We found that Otx2 was essential in septum specification; regulation of Fgf signaling in the rostral telencephalon; and medial ganglionic eminence (MGE) patterning, neurogenesis, and oligodendrogenesis. Within the MGE, Otx2 was required for ventral but not dorsal identity; this is the first demonstration of a transcription factor that contributes to regional patterning within the MGE. Microdissected subpallium (septum, MGE, and LGE ) from wildtype E12.5 CD-1 embryos was used in three independentanti-OTX2 ChIP-seq experiments.
Project description:Heterozygous mutations in the histone acetyltransferase gene KAT6B (MYST4/MORF/QKF) cause cognitive disorders. Congruently, KAT6B is required for brain development, neural stem cell self-renewal and neuronal differentiation in mice. Despite the clear requirement for KAT6B in brain development, its molecular roles remain unexplored. Here we use CUT&Tag sequencing to determine the effects of loss or gain of KAT6B on H3K9ac and H3K23ac histone marks and on RNA Pol II.
Project description:Acetylation of histones by lysine acetyltransferases (KATs) is essential for transcriptional regulation of gene expression. The MYST family of KATs (KAT5-8) includes the oncogenes KAT6A (MOZ) and KAT6B (MORF/QKF). KAT6A has key roles in promoting cell proliferation through transcriptional activation of negative regulators of the Cdkn2a locus, which encode the tumor suppressors INK4A and ARF. To examine the loss of KAT6A function, mouse embryonic fibroblasts (MEFs) were isolated from E13.5 Kat6a+/+ and Kat6a–/– embryos and RNA-seq profiling was performed.
